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Synthesis, In Silico Prediction, and In Vitro Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors
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Introduction:

Allosteric inhibition of EGFR tyrosine kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies.

Methods:

A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR, and HR-mass spectroscopy.

Results:

Compound S4 had a relatively high pharmacophore-fit score, indicating that it may have biological activity similar to the EGFR allosteric inhibitor reference, and it scored a relatively low ΔG against EGFR TK allosteric site, indicating a high likelihood of drug-receptor complex formation. Compound S4 was cytotoxic to the three cancer cell lines tested, particularly HCT-116 colorectal cancer cells, with an IC50 value comparable to Erlotinib. Compound S4 induced the intrinsic apoptotic pathway in HCT-116 cells by arresting them in the G2/M phase. All of the new derivatives, including S4, met the in silico requirements for EGFR allosteric inhibitory activity.

Conclusion:

Compound S4 is a promising EGFR tyrosine kinase allosteric inhibitor that warrants further research.

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Publication Date
Wed Dec 13 2023
Journal Name
2023 3rd International Conference On Intelligent Cybernetics Technology & Applications (icicyta)
GPT-4 versus Bard and Bing: LLMs for Fake Image Detection
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The recent emergence of sophisticated Large Language Models (LLMs) such as GPT-4, Bard, and Bing has revolutionized the domain of scientific inquiry, particularly in the realm of large pre-trained vision-language models. This pivotal transformation is driving new frontiers in various fields, including image processing and digital media verification. In the heart of this evolution, our research focuses on the rapidly growing area of image authenticity verification, a field gaining immense relevance in the digital era. The study is specifically geared towards addressing the emerging challenge of distinguishing between authentic images and deep fakes – a task that has become critically important in a world increasingly reliant on digital med

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Publication Date
Wed Feb 01 2017
Journal Name
Iosr Journal Of Pharmacy And Biological Sciences
Potential Use of Rosemary (Rosmarinus officinalis L.) Essential Oil as Anti-Bacterial and Anti -Algal
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Publication Date
Fri Jan 01 2016
Journal Name
Chemistry And Materials Research
Synthesis of Triazolo and Pyrazolo Derivatives of Quinoline Nucleus
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New heterocyclic derivatives of quinoline are reported. Reaction of quinoline-2-thiol 4 with hydrazine hydrate gave 2-hydrazionoquinoline 5. Treatment of 5 with CS2 in pyridine afforded 1,2,4-triazolo-[4,3-a]- quinolin-1-2H-thione 6, whereas the reaction of 5 with carboxylic acids namely formic acid or acetic acid, yielded the 1,2,4-triazol-[4,3-a]-quinolin 7 or 5-methyl-1,2,4-triazolo [4,3-a]-quinoline 8 through ring closure. Diazotization of 5 under acidic conditions produced the fused tetrazole compound 9, tetrzolo-[1,5-a]- quinoline. Moreover, treatment of 5 with active methlyene compounds gave two pyrazole derivatives 10 and 11. Azomethines 12a-e were prepared through condensation of 5 with aromatic aldehydes or ketones.

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Publication Date
Sun Nov 01 2020
Journal Name
Journal Of Materials Research And Technology
Immobilization of l-asparaginase on gold nanoparticles for novel drug delivery approach as anti-cancer agent against human breast carcinoma cells
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Publication Date
Fri Jan 01 2016
Journal Name
The Journal Of The College Of Basic Education
Polymorphism of IL-4 -590 (C>T) gene in Iraqi children with Type 1 Diabetes Mellitus
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This study included 50 blood serum samples that collected from children with age ranged between 7-12 years. Thirty five samples collected from children with Type 1 Diabetes Mellitus (T1D), and 15 blood serum samples collected from healthy children as a control sample. The polymorphism of IL-4 -590 (C>T) gene, which amplified by using amplification refractory mutation system (ARMS-PCR) was showed high percentage of C allele frequency in T1D patients sample in comparison with T allele frequency, and the C allele revealed as etiological faction with risk by having T1D disease, whereas the T allele showed high frequency from the C allele frequency in control sample, and the T allele revealed as preventive faction from infection by this disease.

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Publication Date
Wed Jan 01 2020
Journal Name
Iop Conference Series: Materials Science And Engineering
Synthesis of anti-corrosion polymers from thiadiazole
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Abstract<p>One of the biggest problems facing many industries particularly oil, is the problem of corrosion, where the metal parts under the influence of the vital factors are eroded during use and storage, therefore, to lift the metal’s ability and to protect it against corrosion, corrosion inhibitors are used. For the first time in this research, polymers which contain sulfur - heterocyclic ring with a thiadiazole base were made. Anti- corrosion polymers were made on two stages, in the first stage, thiadiazole was made from hydrazine hydrate reaction to carbon disulfide, afterwards the first product was reacted with an excess of hydrazine. In the second stage, polymers were prepared by the r</p> ... Show More
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Publication Date
Sat Oct 28 2023
Journal Name
Baghdad Science Journal
Small Nuclear RNA 64 (snoRNA64): A novel Tumor Biomarker for Pancreatic Cancer
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The pancreatic ductal adenocarcinoma (PDAC), which represents over 90% of pancreatic cancer cases,
has the highest proliferative and metastatic rate in comparison to other pancreatic cancer compartments. This
study is designed to determine whether small nucleolar RNA, H/ACA box 64 (snoRNA64) is associated with
pancreatic cancer initiation and progression. Gene expression data from the Gene Expression Omnibus (GEO)
repository have shown that snoRNA64 expression is reduced in primary and metastatic pancreatic cancer as
compared to normal tissues based on statistical analysis of the in Silico analysis. Using qPCR techniques,
pancreatic cancer cell lines include PK-1, PK-8, PK-4, and Mia PaCa-2 with differ

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Publication Date
Thu Mar 31 2022
Journal Name
Journal Of The College Of Education For Women
News of Zubarah Family- Unionists in Nishapur and their Scientific Contributions in the two Centuries (4-6 AH/10-12 AD)
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This research is concerned with qualitatively studying the history of an ancient family, one of the most prominent noble, Alawite families, that assumed the position of the Student Union for the Alawite Supervision in the city of Nishapur in Khorasan during the centries (4-6 H./ 10-12 A.H.). Thus, the research aims to investgate the historical news, and the outstanding Zubarah figures who experience the supereme the religious, historical and scientific position in Khorasan generally and Nishapur particularily. It further aims at arriving at the true meaning of the name Zubarah, and to whom it was called, and the extent of this family’s affiliation to the noble Alawi House, and how they moved to live and settle in the cities of the East

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Publication Date
Wed Aug 10 2011
Journal Name
Ibn Al- Haitham J. For Pure & Appl. S Ci.
A Complete (k,r)-Cap in PG(3,p) Over Galois Field GF(4)
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The aim of t his p aper is t o const ruct t he (k,r)-caps in t he p rojective 3-sp ace PG(3,p ) over Galois field GF(4). We found t hat t he maximum comp let e (k,2)-cap which is called an ovaloid, exist s in PG(3,4) when k = 13. Moreover t he maximum (k,3)-cap s, (k,4)-cap s and (k,5)-caps.

Publication Date
Sun Jun 02 2013
Journal Name
Baghdad Science Journal
Synthesis of New Pyrazoline - Phenoxathiin Derivatives
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Phenoxathiin was prepared by the reaction of diphenyl ether with sulfur in the presence of anhydrous aluminum chloride. This work comprised the synthesis of new phenoxathiin derivatives containing heterocyclic moieties. These heterocyclic compounds were synthesized in three groups. The first group was made up of 2-(oxoalken-1-yl) phenoxathiin derivatives (3a-3j) obtained from the reaction of 2-acetylphenoxathiin with different aromatic aldehyde in the presence of sodium hydroxide. The other two groups involved compounds produced from the reaction of (3a-3j) with hydrazine hydrate in acetic acid to get 2-(1-acetyl pyrazolin-3-yl) phenoxathiin derivatives (4a-4j), and phenyl hydrazine in the presence of piperidine to afford 2-(1-phenyl pyrazo

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